Variant 8-22096507-G-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_022749.7(FHIP2B):c.295G>A(p.Glu99Lys) variant causes a missense, splice region change. The variant allele was found at a frequency of 0.000172 in 1,530,408 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00024 ( 0 hom., cov: 33)

Exomes 𝑓: 0.00016 ( 1 hom. )

Consequence

FHIP2B
NM_022749.7 missense, splice_region

Scores

Splicing: ADA: 0.9473

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.40

Variant links:

Genes affected

FHIP2B (HGNC:16492): (FHF complex subunit HOOK interacting protein 2B)

FHIP2B links:

FHIP2B (HGNC:):

FHIP2B links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.05318439).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FHIP2B	NM_022749.7 linkuse as main transcript	c.295G>A	p.Glu99Lys	missense_variant, splice_region_variant	3/17	ENST00000289921.8	NP_073586.5	Q86V87

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FHIP2B	ENST00000289921.8 linkuse as main transcript	c.295G>A	p.Glu99Lys	missense_variant, splice_region_variant	3/17	5	NM_022749.7	ENSP00000289921.6		Q86V87

Frequencies

GnomAD3 genomes

AF:

0.000237

AC:

AN:

151980

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000131

Gnomad ASJ

AF:

0.00346

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.000246

AC:

AN:

146440

Hom.:

AF XY:

0.000296

AC XY:

AN XY:

77808

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00313

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000481

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000172

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.000165

AC:

227

AN:

1378428

Hom.:

Cov.:

AF XY:

0.000154

AC XY:

104

AN XY:

677182

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.0000293

Gnomad4 ASJ exome

AF:

0.00280

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000392

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000129

Gnomad4 OTH exome

AF:

0.000297

GnomAD4 genome

AF:

0.000237

AC:

AN:

151980

Hom.:

Cov.:

AF XY:

0.000215

AC XY:

AN XY:

74264

show subpopulations

Gnomad4 AFR

AF:

0.000169

Gnomad4 AMR

AF:

0.000131

Gnomad4 ASJ

AF:

0.00346

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000206

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.000328

Hom.:

Bravo

AF:

0.000212

TwinsUK

AF:

0.000809

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000375

AC:

ExAC

AF:

0.000112

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 07, 2022

The c.295G>A (p.E99K) alteration is located in exon 3 (coding exon 3) of the FAM160B2 gene. This alteration results from a G to A substitution at nucleotide position 295, causing the glutamic acid (E) at amino acid position 99 to be replaced by a lysine (K). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.71

BayesDel_addAF

Benign

-0.20

BayesDel_noAF

Benign

-0.21

CADD

Pathogenic

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.15

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.44

FATHMM_MKL

Uncertain

0.94

LIST_S2

Uncertain

0.96

M_CAP

Benign

0.039

MetaRNN

Benign

0.053

MetaSVM

Benign

-0.47

MutationAssessor

Uncertain

2.4

PrimateAI

Uncertain

0.76

PROVEAN

Uncertain

-2.8

REVEL

Benign

0.28

Sift

Uncertain

0.0060

Sift4G

Uncertain

0.012

Polyphen

0.96

Vest4

0.43

MVP

0.82

MPC

0.13

ClinPred

0.24

GERP RS

5.0

Varity_R

0.39

gMVP

0.40

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.95

dbscSNV1_RF

Pathogenic

0.79

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over